Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet

Brent J.F. Hill, Joseph L. Dixon, Michael Sturek

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Intracellular Ca2+ store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca2+ uptake into intracellular Ca2+ stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks - (1) low fat fed (control); (2) hyperlipidemic (F); (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the myoplasmic Ca2+ (Cam) response measured using single cell fura-2 imaging. The Cam response to caffeine (5 mM to release Ca2+ from the sarcoplasmic reticulum, SR) and ionomycin (10 μM; to release the total Ca2+ store) was determined in either the presence of low Na (19Na; inhibits Na+-Ca2+ exchange), thapsigargin (TSG; inhibits the SR Ca2+ pump), and a 19Na + TSG solution. Low Na induced the uptake of Ca2+ into both SR and non-SR Ca2+ stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca2+ store with TSG, 19Na evoked Ca2+ uptake into non-SR Ca2+ stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca2+ by SR and non-SR Ca2+ stores in diabetic dyslipidemic pigs.

Original languageEnglish (US)
Pages (from-to)117-124
Number of pages8
JournalAtherosclerosis
Volume159
Issue number1
DOIs
StatePublished - Nov 10 2001

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Keywords

  • Calcium
  • Dyslipidemia
  • HMG-CoA reductase
  • Ionomycin
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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